102438-99-3Relevant academic research and scientific papers
Silicon analogues of the nonpeptidic GnRH antagonist AG-045572: Syntheses, crystal structure analyses, and pharmacological characterization
Barnes, Matthew J.,Burschka, Christian,Buettner, Matthias W.,Conroy, Richard,Daiss, Juergen O.,Gray, Ian C.,Hendrick, Alan G.,Tam,Kuehn, Diana,Miller, David J.,Mills, John S.,Mitchell, Philip,Montana, John G.,Muniandy, Parameswary A.,Rapley, Helen,Showell, Graham A.,Tebbe, David,Tacke, Reinhold,Warneck, Julie B.H.,Zhu, Bin
, p. 2070 - 2080 (2011)
AG-045572 (CMPD1, 1a) is a nonpeptidic gonadotropin-releasing hormone (GnRH) antagonist that has been investigated for the treatment of sex hormone-related diseases. In the context of systematic studies on sila-substituted drugs, the silicon analogue disila-AG-045572 (1b) and its derivative 2 were prepared in multi-step syntheses and characterized by elemental analyses (C, H, N), NMR spectroscopic studies (1H, 13C, 29Si), and single-crystal X-ray diffraction. The pharmacological properties of compounds 1a, 1b, and 2 were compared in terms of their in vitro potency at cloned human and rat GnRH receptors. Compounds 1a and 2 were also examined in regard to their pharmacokinetics and in vivo efficacy in both castrated rat (luteinizing hormone (LH) suppression) and intact rat (testosterone suppression) models. The efficacy and pharmacokinetic profiles of 1a and its silicon-containing analogue 2 appear similar, indicating that replacement of the 5,6,7,8-tetrahydronaphthalene ring system by the 1,3-disilaindane skeleton led to retention of efficacy. Therefore, the silicon compound 2 represents a novel drug prototype for the design of potent, orally available GnRH antagonists suitable for once-daily dosing.
HETEROCYCLIC SILICON COMPOUNDS AND THEIR USE IN THE TREATMENT OF DISEASES OR CONDITIONS ASSOCIATED WITH GNRH (GONADOTROPIN-RELEASING HORMONE)
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Page/Page column 17, (2010/02/07)
A compound of formula (I) wherein one of X and Y is silicon, and the other is carbon or silicon; Z is oxygen, sulphur or -N(R)-, wherein R is hydrogen or alkyl; R1 is hydrogen, halogen, alkyl, alkenyl, alkynyl, alkoxy or cycloalkyl; and R2 is alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, -alkyl-cycloalkyl, -alkyl-heterocycloalkyl, -alkyl-aryl or -alkyl-heteroaryl; or a pharmaceutically acceptable salt thereof. The compounds are used in the manufacture of a medicament for the treatment or prevention of a disease or condition associated with GnRH (gonadotropin-releasing hormone), e.g. for the treatment or prevention of progression of cancer (e.g. leukaemia therapy), of a fertility disorder, of HIV infection or AIDS, of Alzheimer’s disease of fibrosis, of endometriosis, of uterine fibroids or of uterine leiomyoma.
